Cancer affects people at all ages with the risk for most types increasing with age. Cancers are mainly due to genetic deregulations of cells and to lifestyle and environmental factors, which cause abnormalities in the genetic material of cells. For example brain tumours make up to 2% of all tumours in adults and, in their malignant form (grade IV or glioblastoma (GBM)) remain one of the most aggressive diseases with a 2-years survival rate of 32% with today's available standard treatments. It is reported that 1 out of 166 humans are diagnosed with brain tumour once in their lifetime (lifetime risk). Although combining chemotherapy with radiation shows a significant benefit for patients suffering from glioblastoma (GBM), the mean survival rate remains dismal, 16 months on average. Neither genetic factors nor environmental risk factors have been identified and little is known about the biological mechanisms involved in the initiation and progression phases of these brain tumours.
The treatment of cancers is one of the most heavily investigated areas in biomedical research today. Although many anticancer drugs have been and continue to be discovered, there remains the immense problem of developing drugs which will efficiently address this disease and avoid it recurrence.
Many current therapeutic strategies make the assumption that the biology and metabolism of every single cancer cell, including glioma cells, is similar and unfortunately did not provide a significant progress in the treatment of cancers, including glioma.
The recent identification of Stem-like Cells (SC) in a number of human cancers like acute myeloid leukemias (AML), breast, melanoma, colon and brain tumours has renewed interest in the hypothesis that cancers may arise from somatic mutations in adult stem/progenitor cells. A minor population of cancer stem-like cells is likely to represent the source of tumour cell expansion, recurrence and metastasis, thus determining the biological behaviour of tumours including proliferation, progression, and subsequently response to therapy.
Targeting tumour-initiating cells remains challenging due to their rarity, instability in culture and the absence of robust tracer agents. So far, no efficient treatment against tumour-initiating cells has shown a complete eradication of the tumour growth or absence of recurrence in any of the orthotopic xenograft and/or transgenic mouse model. The resistance of tumour-initiating cells to conventional radiotherapy has been demonstrated (Bao et al., 2006; Clement et al., 2007). For example it is known that glioma-initiating cells are resistant to chemotherapeutic agents like temozolomide. These data might explain the inevitable recurrence of gliomas and define tumour-initiating cells as novel targets to overcome the resistance to conventional therapy in this disease.
Because it was shown that tumour-initiating cells (TICs) are actively chemo- and radio-resistant, including brain tumours, there is therefore a need to develop new active agents against the TICs reservoir which may be useful in the treatment of such cancers presenting tumour-initiating cells.